Abstract
X-ray structures of the GluR2 ligand-binding core in complex with (S)-Des-Me-AMPA and in the presence and absence of zinc ions have been determined. (S)-Des-Me-AMPA, which is devoid of a substituent in the 5-position of the isoxazolol ring, only has limited interactions with the partly hydrophobic pocket of the ligand-binding site, and adopts an AMPA-like binding mode. The structures, in comparison with other agonist complex structures, disclose the relative importance of the isoxazolol ring and of the substituent in the 5-position for the mode of binding. A relationship appears to exist between the extent of interaction of the ligand with the hydrophobic pocket and the affinity of the ligand.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites
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Crystallography, X-Ray
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Hydrogen Bonding
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Hydrophobic and Hydrophilic Interactions
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Isoxazoles / chemistry*
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Ligands
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Macromolecular Substances
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Methionine / chemistry
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Models, Molecular
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Peptides / chemistry
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Protein Binding
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Receptors, AMPA / agonists*
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Receptors, AMPA / chemistry*
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Receptors, AMPA / metabolism
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Sulfates / chemistry
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Zinc / chemistry
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / analogs & derivatives
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / chemistry*
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / metabolism*
Substances
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2-amino-3-(3-hydroxy-4-isoxazoyl)propionic acid
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Isoxazoles
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Ligands
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Macromolecular Substances
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Peptides
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Receptors, AMPA
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Sulfates
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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Methionine
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Zinc
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glutamate receptor ionotropic, AMPA 2